1. Field of the Invention
This invention relates to a fluorescence imaging apparatus for performing an imaging operation for detecting a fluorescence image formed with fluorescence, which has been produced from a measuring site when excitation light is irradiated to the measuring site, and an imaging operation for detecting an ordinary image formed with reflected light, which has been reflected by the measuring site when illumination light is irradiated to the measuring site.
2. Description of the Related Art
It has heretofore been known that, in cases where excitation light having wavelengths falling within an excitation wavelength range for an intrinsic dye in a living body is irradiated to the living body, a fluorescence spectrum of fluorescence produced by the intrinsic dye in the living body varies for normal tissues and diseased tissues. FIG. 9 shows typical fluorescence spectra of the fluorescence produced from normal tissues and the fluorescence produced from diseased tissues, which fluorescence spectra have been measured by the inventors. As illustrated in FIG. 9, the fluorescence produced from the normal tissues has a high light intensity as a whole and has a particularly high light intensity at a blue wavelength region. Also, the fluorescence produced from the diseased tissues has a low light intensity as a whole and has a flat spectral pattern. It is assumed that the thus produced fluorescence results from superposition of the fluorescence produced by various kinds of intrinsic dyes in the living body, such as FAD, collagen, fibronectin, and porphyrin.
There have heretofore been proposed systems wherein, by the utilization of the characteristics such that the fluorescence spectrum of the fluorescence produced by the intrinsic dye in the living body varies for the normal tissues and the diseased tissues, the fluorescence, which has been produced from a measuring site in a living body when the excitation light is irradiated to the measuring site, is imaged, the thus detected fluorescence image is displayed as a color image or a pseudo color image on a monitor, and location and an infiltration range of the diseased tissues are thereby displayed as a change in color. In such systems, fluorescence imaging apparatuses for imaging the fluorescence, which has been produced from the measuring site in the living body when the excitation light is irradiated to the measuring site, are utilized.
Ordinarily, the fluorescence imaging apparatuses comprise illumination means for irradiating white illumination light to the measuring site, excitation light irradiating means for irradiating the excitation light to the measuring site, and imaging means for performing imaging operations for detecting an ordinary image and a fluorescence image. FIG. 10 is a timing chart showing timings, with which imaging operations are performed in conventional fluorescence imaging apparatuses. As illustrated in FIG. 10, in the conventional fluorescence imaging apparatuses, the irradiation of the white light and the irradiation of the excitation light are switched between each other with manual operations or at predetermined intervals, and the fluorescence image or the ordinary image is displayed as a dynamic image on the monitor.
With the conventional fluorescence imaging apparatuses described above, only either one of the ordinary image and the fluorescence image is displayed on the monitor. Therefore, the problems occur in that, for example, when a person, who sees the displayed image, finds the presence of the diseased tissues from the displayed fluorescence image and changes over the imaging operation from the detection of the fluorescence image to the detection of the ordinary image in order to perform treatment, it becomes impossible to find the position of the diseased tissues. In order for the problems described above to be eliminated, there is a strong demand for a fluorescence imaging apparatus, with which both the fluorescence image and the ordinary image are capable of being displayed simultaneously as real-time dynamic images on a monitor.
In order for the dynamic images of the fluorescence image and the ordinary image to be displayed simultaneously on a monitor, it may be considered to provide ordinary imaging means for performing the imaging operation for detecting the ordinary image and fluorescence imaging means for performing the imaging operation for detecting the fluorescence image as two independent means, and to alternately perform operations for irradiating the illumination light and detecting the ordinary image and operations for irradiating the excitation light and detecting the fluorescence image in a time division mode.
However, in order for both the ordinary image and the fluorescence image to be displayed as the dynamic images, it is necessary that the imaging operation for detecting the ordinary image and the imaging operation for detecting the fluorescence image be changed over quickly. In such cases, it is not always possible to utilize a mechanical shutter, and the like. Also, the problems occur in that, when the illumination light is being irradiated to the measuring site and the ordinary image is being detected by the ordinary imaging means, the reflected light of the illumination light also impinges upon the fluorescence imaging means. As a result, the imaging operation for detecting the fluorescence image cannot be performed accurately.
Further, the problems occur in that, when the fluorescence image is being detected by the fluorescence imaging means, the reflected light of the excitation light also impinges upon the ordinary imaging means. As a result, the imaging operation for detecting the ordinary image cannot be performed accurately.
The primary object of the present invention is to provide a fluorescence imaging apparatus, wherein ordinary imaging means for performing an imaging operation for detecting an ordinary image and fluorescence imaging means for performing an imaging operation for detecting a fluorescence image are provided as two independent means, and a combination of irradiation of illumination light and an imaging operation for detecting the ordinary image and a combination of irradiation of excitation light and an imaging operation for detecting the fluorescence image are performed alternately in a time division mode, such that the imaging operation for detecting the fluorescence image is not adversely affected by reflected light of the illumination light, which reflected light impinges upon the fluorescence imaging means when the imaging operation for detecting the ordinary image is being performed, and such that a sharp fluorescence image is capable of being detected.
Another object of the present invention is to provide a fluorescence imaging apparatus, wherein an imaging operation for detecting an ordinary image is not adversely affected by reflected light of excitation light, which reflected light impinges upon ordinary imaging means when an imaging operation for detecting a fluorescence image is being performed, and a sharp ordinary image is capable of being detected.
The present invention provides a first fluorescence imaging apparatus, comprising:
i) excitation light irradiating means for irradiating excitation light to a measuring site, the excitation light causing the measuring site to produce fluorescence,
ii) fluorescence imaging means for performing an imaging operation for detecting a fluorescence image formed with the fluorescence, which has been produced from the measuring site when the excitation light is irradiated to the measuring site,
iii) illumination means for irradiating illumination light to the measuring site,
iv) ordinary imaging means for performing an imaging operation for detecting an ordinary image formed with reflected light of the illumination light, which reflected light has been reflected by the measuring site when the illumination light is irradiated to the measuring site, and
v) control means for controlling operations of the excitation light irradiating means, the fluorescence imaging means, the illumination means, and the ordinary imaging means, such that the imaging operation for detecting the fluorescence image and the imaging operation for detecting the ordinary image are performed alternately,
wherein the control means controls such that an operation for throwing off accumulated electric charges is performed before the imaging operation of the fluorescence imaging means is performed and/or before the imaging operation of the ordinary imaging means is performed.
The present invention also provides a second fluorescence imaging apparatus, comprising:
i) excitation light irradiating means for irradiating excitation light to a measuring site, the excitation light causing the measuring site to produce fluorescence,
ii) fluorescence imaging means for performing an imaging operation for detecting a fluorescence image formed with the fluorescence, which has been produced from the measuring site when the excitation light is irradiated to the measuring site,
iii) illumination means for irradiating illumination light to the measuring site,
iv) ordinary imaging means for performing an imaging operation for detecting an ordinary image formed with reflected light of the illumination light, which reflected light has been reflected by the measuring site when the illumination light is irradiated to the measuring site, and
v) control means for controlling operations of the excitation light irradiating means, the fluorescence imaging means, the illumination means, and the ordinary imaging means, such that the imaging operation for detecting the fluorescence image and the imaging operation for detecting the ordinary image are performed alternately,
wherein the ordinary imaging means is provided with excitation light removing means for removing the excitation light from light impinging upon the ordinary imaging means.
The present invention further provides a third fluorescence imaging apparatus, comprising:
i) excitation light irradiating means for irradiating excitation light to a measuring site, the excitation light causing the measuring site to produce fluorescence,
ii) fluorescence imaging means for performing an imaging operation for detecting a fluorescence image formed with the fluorescence, which has been produced from the measuring site when the excitation light is irradiated to the measuring site,
iii) illumination means for irradiating illumination light to the measuring site,
iv) ordinary imaging means for performing an imaging operation for detecting an ordinary image formed with reflected light of the illumination light, which reflected light has been reflected by the measuring site when the illumination light is irradiated to the measuring site, and
v) control means for controlling operations of the excitation light irradiating means, the fluorescence imaging means, the illumination means, and the ordinary imaging means, such that the imaging operation for detecting the fluorescence image and the imaging operation for detecting the ordinary image are performed alternately,
wherein the ordinary imaging means is provided with excitation light removing means for removing the excitation light from light impinging upon the ordinary imaging means, and
the control means controls such that an operation for throwing off accumulated electric charges is performed before the imaging operation of the fluorescence imaging means is performed.
In the second and third fluorescence imaging apparatuses in accordance with the present invention, the excitation light removing means should preferably be an excitation light cut-off filter for transmitting only light having wavelengths falling within a wavelength region other than the wavelength region of the excitation light.
In the first and third fluorescence imaging apparatuses in accordance with the present invention, the operation for throwing off the accumulated electric charges should preferably be a dummy reading operation.
Also, the first and third fluorescence imaging apparatuses in accordance with the present invention should preferably be modified such that the fluorescence imaging means and/or the ordinary imaging means comprises a substrate and an image sensor formed on the substrate, and the operation for throwing off the accumulated electric charges is an operation for sweeping out unnecessary electric charges toward the substrate direction.
The illumination light is utilized for illuminating the measuring site in order for the ordinary image to be detected. As the illumination light, one of various kinds of light enabling the ordinary image to be detected may be utilized. For example, in cases where a simultaneous mode technique, in which an on-chip color filter is employed, is utilized for the imaging operation for detecting the ordinary image, white light may be utilized as the illumination light. In cases where a surface sequential technique for successively detecting three-color light images is utilized for the imaging operation for detecting the ordinary image, three-color surface sequential light beams, which are irradiated successively, may be utilized as the illumination light.
The dummy reading operation may be one of various operations for reading unnecessary electric charges, which have been accumulated in the imaging means, and preventing the thus read unnecessary electric charges from being subjected to regular signal processing. For example, the dummy reading operation may be a reading operation wherein, after the unnecessary electric charges have been read, writing of a signal, which is formed with the unnecessary electric charges, into a memory is not performed in a subsequent processing circuit. Alternatively, the dummy reading operation may be a reading operation wherein, after the unnecessary electric charges have been read, the unnecessary electric charges are erased to the ground at a subsequent stage.
With the first fluorescence imaging apparatus in accordance with the present invention, the control means for controlling the operations of the excitation light irradiating means, the fluorescence imaging means, the illumination means, and the ordinary imaging means, controls such that the operation for throwing off the accumulated electric charges is performed before the imaging operation of the fluorescence imaging means is performed. Therefore, the electric charges having been accumulated in the fluorescence imaging means due to the reflected light of the illumination light, which reflected light impinges upon the fluorescence imaging means when the imaging operation for detecting the ordinary image is performed, are thrown off before the imaging operation for detecting the fluorescence image is performed. Accordingly, the imaging operation for detecting the fluorescence image is not affected by the electric charges described above, and a sharp fluorescence image is capable of being detected.
Also, with the first fluorescence imaging apparatus in accordance with the present invention, the control means controls such that the operation for throwing off the accumulated electric charges is performed before the imaging operation of the ordinary imaging means is performed. Therefore, the electric charges having been accumulated in the ordinary imaging means due to the reflected light of the excitation light, which reflected light impinges upon the ordinary imaging means when the imaging operation for detecting the fluorescence image is performed, are thrown off before the imaging operation for detecting the ordinary image is performed. Accordingly, the imaging operation for detecting the ordinary image is not affected by the electric charges described above, and a sharp ordinary image is capable of being detected.
With the second fluorescence imaging apparatus in accordance with the present invention, wherein the ordinary imaging means is provided with the excitation light removing means for removing the excitation light from the light impinging upon the ordinary imaging means, the reflected light of the excitation light is capable of being prevented from entering into the ordinary imaging means when the imaging operation for detecting the fluorescence image is performed. Therefore, the imaging operation for detecting the ordinary image is not affected by the reflected light of the excitation light, and a sharp ordinary image is capable of being detected.
Also, in such cases, the fluorescence, which has been produced from the measuring site when the excitation light is irradiated to the measuring site, also impinges upon the ordinary imaging means. However, the light intensity of the fluorescence is lower than the light intensity of the reflected light of the illumination light, which reflected light impinges upon the ordinary imaging means when the imaging operation for detecting the ordinary image is performed. Therefore, little effect occurs upon the imaging operation for detecting the ordinary image.
With the third fluorescence imaging apparatus in accordance with the present invention, the ordinary imaging means is provided with the excitation light removing means for removing the excitation light from the light impinging upon the ordinary imaging means. Also, the control means controls such that the operation for throwing off the accumulated electric charges is performed before the imaging operation of the fluorescence imaging means is performed. Therefore, the reflected light of the excitation light is capable of being prevented from entering into the ordinary imaging means when the imaging operation for detecting the fluorescence image is performed. Also, the electric charges having been accumulated in the fluorescence imaging means due to the reflected light of the illumination light, which reflected light impinges upon the fluorescence imaging means when the imaging operation for detecting the ordinary image is performed, are thrown off before the imaging operation for detecting the fluorescence image is performed. Accordingly, a sharp ordinary image and a sharp fluorescence image are capable of being detected.
With the second and third fluorescence imaging apparatuses in accordance with the present invention, wherein the excitation light removing means is the excitation light cut-off filter for transmitting only light having wavelengths falling within a wavelength region other than the wavelength region of the excitation light, with the simple constitution, the reflected light of the excitation light is capable of being prevented from entering into the ordinary imaging means when the imaging operation for detecting the fluorescence image is performed.
With the first and third fluorescence imaging apparatuses in accordance with the present invention, wherein the operation for throwing off the accumulated electric charges is the dummy reading operation, the reading operation under the control of the control means need not be altered markedly between when the ordinary reading operation is performed and when the dummy reading operation is performed. Therefore, the constitution of the control means is capable of being simplified.
With the first and third fluorescence imaging apparatuses in accordance with the present invention, the fluorescence imaging means and/or the ordinary imaging means may comprise the substrate and the image sensor formed on the substrate, and the operation for throwing off the accumulated electric charges may be the operation for sweeping out the unnecessary electric charges toward the substrate direction. In such cases, the timing, with which the unnecessary electric charges are swept out, is capable of being set arbitrarily. Therefore, the imaging time is capable of being set arbitrarily in accordance with imaging conditions.